Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

Peter J. Dyck; John C. Kincaid; P. James B. Dyck; Vinay Chaudhry; Namita A. Goyal; Christina Alves; Hayet Salhi; Janice F. Wiesman; Celine Labeyrie; Jessica Robinson-Papp; Márcio Cardoso; Matilde Laura; Katherine Ruzhansky; Andrea Cortese; Thomas H. Brannagan; Julie Khoury; Sami Khella; Márcia Waddington-Cruz; João Ferreira; Annabel K. Wang; Marcus V. Pinto; Samar S. Ayache; Merrill D. Benson; John L. Berk; Teresa Coelho; Michael Polydefkis; Peter Gorevic; David H. Adams; Violaine Plante-Bordeneuve; Carol Whelan; Giampaolo Merlini; Stephen Heitner; Brian M. Drachman; Isabel Conceição; Christopher J. Klein; Morie A. Gertz; Elizabeth J. Ackermann; Steven G. Hughes; Michelle L. Mauermann; Rito Bergemann; Karen A. Lodermeier; Jenny L. Davies; Rickey E. Carter; William J. Litchy

doi:10.1002/mus.25563

Assessing mNIS+7_Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

Peter J. Dyck, John C. Kincaid, P. James B. Dyck, Vinay Chaudhry, Namita A. Goyal, Christina Alves, Hayet Salhi, Janice F. Wiesman, Celine Labeyrie, Jessica Robinson-Papp, Márcio Cardoso, Matilde Laura, Katherine Ruzhansky, Andrea Cortese, Thomas H. Brannagan, Julie Khoury, Sami Khella, Márcia Waddington-Cruz, João Ferreira, Annabel K. WangMarcus V. Pinto, Samar S. Ayache, Merrill D. Benson, John L. Berk, Teresa Coelho, Michael Polydefkis, Peter Gorevic, David H. Adams, Violaine Plante-Bordeneuve, Carol Whelan, Giampaolo Merlini, Stephen Heitner, Brian M. Drachman, Isabel Conceição, Christopher J. Klein, Morie A. Gertz, Elizabeth J. Ackermann, Steven G. Hughes, Michelle L. Mauermann, Rito Bergemann, Karen A. Lodermeier, Jenny L. Davies, Rickey E. Carter, William J. Litchy

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Introduction: Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7_Ionis), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. Methods: We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7_Ionis) and its subscores and correlation with disability and health scores. Results: The mNIS+7_Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. Conclusions: Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7_Ionis, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901–911, 2017.

Original language	English (US)
Pages (from-to)	901-911
Number of pages	11
Journal	Muscle and Nerve
Volume	56
Issue number	5
DOIs	https://doi.org/10.1002/mus.25563
State	Published - Nov 2017

Keywords

disability
familial amyloidotic polyneuropathy (FAP)
neurophysiologic tests
oligonucleotide trials
peripheral neuropathy
polyneuropathy signs
proficiency

ASJC Scopus subject areas

Physiology
Clinical Neurology
Cellular and Molecular Neuroscience
Physiology (medical)

Access to Document

10.1002/mus.25563

Cite this

Dyck, P. J., Kincaid, J. C., Dyck, P. J. B., Chaudhry, V., Goyal, N. A., Alves, C., Salhi, H., Wiesman, J. F., Labeyrie, C., Robinson-Papp, J., Cardoso, M., Laura, M., Ruzhansky, K., Cortese, A., Brannagan, T. H., Khoury, J., Khella, S., Waddington-Cruz, M., Ferreira, J., ... Litchy, W. J. (2017). Assessing mNIS+7_Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial. Muscle and Nerve, 56(5), 901-911. https://doi.org/10.1002/mus.25563

Dyck, PJ, Kincaid, JC, Dyck, PJB, Chaudhry, V, Goyal, NA, Alves, C, Salhi, H, Wiesman, JF, Labeyrie, C, Robinson-Papp, J, Cardoso, M, Laura, M, Ruzhansky, K, Cortese, A, Brannagan, TH, Khoury, J, Khella, S, Waddington-Cruz, M, Ferreira, J, Wang, AK, Pinto, MV, Ayache, SS, Benson, MD, Berk, JL, Coelho, T, Polydefkis, M, Gorevic, P, Adams, DH, Plante-Bordeneuve, V, Whelan, C, Merlini, G, Heitner, S, Drachman, BM, Conceição, I, Klein, CJ, Gertz, MA, Ackermann, EJ, Hughes, SG, Mauermann, ML, Bergemann, R, Lodermeier, KA, Davies, JL, Carter, RE & Litchy, WJ 2017, 'Assessing mNIS+7_Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial', Muscle and Nerve, vol. 56, no. 5, pp. 901-911. https://doi.org/10.1002/mus.25563

@article{ed2cdcdec58145f3a5be2b326d9a4c52,

title = "Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial",

abstract = "Introduction: Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. Methods: We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis) and its subscores and correlation with disability and health scores. Results: The mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. Conclusions: Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901–911, 2017.",

keywords = "disability, familial amyloidotic polyneuropathy (FAP), neurophysiologic tests, oligonucleotide trials, peripheral neuropathy, polyneuropathy signs, proficiency",

author = "Dyck, {Peter J.} and Kincaid, {John C.} and Dyck, {P. James B.} and Vinay Chaudhry and Goyal, {Namita A.} and Christina Alves and Hayet Salhi and Wiesman, {Janice F.} and Celine Labeyrie and Jessica Robinson-Papp and M{\'a}rcio Cardoso and Matilde Laura and Katherine Ruzhansky and Andrea Cortese and Brannagan, {Thomas H.} and Julie Khoury and Sami Khella and M{\'a}rcia Waddington-Cruz and Jo{\~a}o Ferreira and Wang, {Annabel K.} and Pinto, {Marcus V.} and Ayache, {Samar S.} and Benson, {Merrill D.} and Berk, {John L.} and Teresa Coelho and Michael Polydefkis and Peter Gorevic and Adams, {David H.} and Violaine Plante-Bordeneuve and Carol Whelan and Giampaolo Merlini and Stephen Heitner and Drachman, {Brian M.} and Isabel Concei{\c c}{\~a}o and Klein, {Christopher J.} and Gertz, {Morie A.} and Ackermann, {Elizabeth J.} and Hughes, {Steven G.} and Mauermann, {Michelle L.} and Rito Bergemann and Lodermeier, {Karen A.} and Davies, {Jenny L.} and Carter, {Rickey E.} and Litchy, {William J.}",

note = "Funding Information: Conflicts of Interest: None of the authors report a conflict of interest. P.J. Dyck receives grants in support of research from Ionis, Inc., and Alnylam, Inc., and honoraria for research teaching. He previously received NIH support (NS 14304) used to develop healthy subject reference values of neurophysiologic tests used in this study. J. Robinson-Papp receives NIH support (R21 DK105917 and U24 MH100931). E.J. Ackermann and S.G. Hughes are employees and shareholders of Ionis Pharmaceuticals. R. Bergemann is an employee of GlaxoSmithKline, Inc. V. Plante-Bordeneuve receives honoraria for participation on an advisory board for Ionis, Inc. and Pfizer and travel and meeting expenses supported by Pfizer, Inc. The other co-authors report no financial disclosures other than support for the IONIS-TTRRxtrial reported here. Funding Information: Abbreviations: ATTR, transthyretin amyloidosis; CMAP, compound muscle action potential; FAP, familial amyloidotic polyneuropathy; HP5, heat as pain 5 (of 1–10 severity) as tested by CASE IVc, WR Medical Electronics; Maplewood, Minnesota; HRdb, heart rate decrease with deep breathing; INCAT, Inflammatory Neuropathy Cause and Treatment; MC PNRL, Mayo Clinic Peripheral Nerve Research Lab; MNCV, motor nerve conduction velocity; MNDL, motor nerve distal latency; mNIS17Ionis, modified NIS17 score (neurophysiologic tests used in Ionis-TTRRX clinical trial in FAP); NC, nerve conduction; ND, normal deviate; NIS, Neuropathy Impairment Score; NIS-R, NIS of muscle stretch reflexes; NIS-S, NIS of clinical sensation of toes and fingers; NIS-W, NIS of weakness; Norfolk Quality of Life-Diabetic Neuropathy, Norfolk QOL-DN (a health score); NSC, Neuropathy Symptoms and Change score (a health score); PND, polyneuropathy disability score, also called amyloid gait stage; SF-36, 36-Item Short Form Health Survey (a health score); S ST QSTing, Smart Somatotopic Quantitative Sensation Testing using CASE IVc, WR Medical Electronics, Maplewood, Minnesota; SNAP, sensory nerve action potential; TP, touch-pressure; TTR, transthyretin; VDT, vibratory detection threshold. Key words: disability; familial amyloidotic polyneuropathy (FAP); neurophysiologic tests; oligonucleotide trials; peripheral neuropathy; polyneuropathy signs; proficiency Funding: Financial support for the study provided by Ionis Pharmaceutical Inc. Carlsbad, California. Reference values for attributes of nerve conduction, quantitative sensation tests, and for other neurophysiologic tests were obtained from a grant from the National Institute of Neurological Disorders and Stroke (14304) and from Mayo Foundation. Study data were collected and managed using REDCap electronic data capture tools hosted at Mayo Clinic, Center for Clinical and Translational Science grant support (UL1 TR000135). Funding Information: Financial support for the study provided by Ionis Pharmaceutical Inc. Carlsbad, California. Reference values for attributes of nerve conduction, quantitative sensation tests, and for other neurophysiologic tests were obtained from a grant from the National Institute of Neurological Disorders and Stroke (14304) and from Mayo Foundation. Study data were collected and managed using REDCap electronic data capture tools hosted at Mayo Clinic, Center for Clinical and Translational Science grant support (UL1 TR000135). Publisher Copyright: {\textcopyright} 2017 Wiley Periodicals, Inc.",

year = "2017",

month = nov,

doi = "10.1002/mus.25563",

language = "English (US)",

volume = "56",

pages = "901--911",

journal = "Muscle and Nerve",

issn = "0148-639X",

publisher = "John Wiley and Sons Inc.",

number = "5",

}

TY - JOUR

T1 - Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

AU - Dyck, Peter J.

AU - Kincaid, John C.

AU - Dyck, P. James B.

AU - Chaudhry, Vinay

AU - Goyal, Namita A.

AU - Alves, Christina

AU - Salhi, Hayet

AU - Wiesman, Janice F.

AU - Labeyrie, Celine

AU - Robinson-Papp, Jessica

AU - Cardoso, Márcio

AU - Laura, Matilde

AU - Ruzhansky, Katherine

AU - Cortese, Andrea

AU - Brannagan, Thomas H.

AU - Khoury, Julie

AU - Khella, Sami

AU - Waddington-Cruz, Márcia

AU - Ferreira, João

AU - Wang, Annabel K.

AU - Pinto, Marcus V.

AU - Ayache, Samar S.

AU - Benson, Merrill D.

AU - Berk, John L.

AU - Coelho, Teresa

AU - Polydefkis, Michael

AU - Gorevic, Peter

AU - Adams, David H.

AU - Plante-Bordeneuve, Violaine

AU - Whelan, Carol

AU - Merlini, Giampaolo

AU - Heitner, Stephen

AU - Drachman, Brian M.

AU - Conceição, Isabel

AU - Klein, Christopher J.

AU - Gertz, Morie A.

AU - Ackermann, Elizabeth J.

AU - Hughes, Steven G.

AU - Mauermann, Michelle L.

AU - Bergemann, Rito

AU - Lodermeier, Karen A.

AU - Davies, Jenny L.

AU - Carter, Rickey E.

AU - Litchy, William J.

N1 - Funding Information: Conflicts of Interest: None of the authors report a conflict of interest. P.J. Dyck receives grants in support of research from Ionis, Inc., and Alnylam, Inc., and honoraria for research teaching. He previously received NIH support (NS 14304) used to develop healthy subject reference values of neurophysiologic tests used in this study. J. Robinson-Papp receives NIH support (R21 DK105917 and U24 MH100931). E.J. Ackermann and S.G. Hughes are employees and shareholders of Ionis Pharmaceuticals. R. Bergemann is an employee of GlaxoSmithKline, Inc. V. Plante-Bordeneuve receives honoraria for participation on an advisory board for Ionis, Inc. and Pfizer and travel and meeting expenses supported by Pfizer, Inc. The other co-authors report no financial disclosures other than support for the IONIS-TTRRxtrial reported here. Funding Information: Abbreviations: ATTR, transthyretin amyloidosis; CMAP, compound muscle action potential; FAP, familial amyloidotic polyneuropathy; HP5, heat as pain 5 (of 1–10 severity) as tested by CASE IVc, WR Medical Electronics; Maplewood, Minnesota; HRdb, heart rate decrease with deep breathing; INCAT, Inflammatory Neuropathy Cause and Treatment; MC PNRL, Mayo Clinic Peripheral Nerve Research Lab; MNCV, motor nerve conduction velocity; MNDL, motor nerve distal latency; mNIS17Ionis, modified NIS17 score (neurophysiologic tests used in Ionis-TTRRX clinical trial in FAP); NC, nerve conduction; ND, normal deviate; NIS, Neuropathy Impairment Score; NIS-R, NIS of muscle stretch reflexes; NIS-S, NIS of clinical sensation of toes and fingers; NIS-W, NIS of weakness; Norfolk Quality of Life-Diabetic Neuropathy, Norfolk QOL-DN (a health score); NSC, Neuropathy Symptoms and Change score (a health score); PND, polyneuropathy disability score, also called amyloid gait stage; SF-36, 36-Item Short Form Health Survey (a health score); S ST QSTing, Smart Somatotopic Quantitative Sensation Testing using CASE IVc, WR Medical Electronics, Maplewood, Minnesota; SNAP, sensory nerve action potential; TP, touch-pressure; TTR, transthyretin; VDT, vibratory detection threshold. Key words: disability; familial amyloidotic polyneuropathy (FAP); neurophysiologic tests; oligonucleotide trials; peripheral neuropathy; polyneuropathy signs; proficiency Funding: Financial support for the study provided by Ionis Pharmaceutical Inc. Carlsbad, California. Reference values for attributes of nerve conduction, quantitative sensation tests, and for other neurophysiologic tests were obtained from a grant from the National Institute of Neurological Disorders and Stroke (14304) and from Mayo Foundation. Study data were collected and managed using REDCap electronic data capture tools hosted at Mayo Clinic, Center for Clinical and Translational Science grant support (UL1 TR000135). Funding Information: Financial support for the study provided by Ionis Pharmaceutical Inc. Carlsbad, California. Reference values for attributes of nerve conduction, quantitative sensation tests, and for other neurophysiologic tests were obtained from a grant from the National Institute of Neurological Disorders and Stroke (14304) and from Mayo Foundation. Study data were collected and managed using REDCap electronic data capture tools hosted at Mayo Clinic, Center for Clinical and Translational Science grant support (UL1 TR000135). Publisher Copyright: © 2017 Wiley Periodicals, Inc.

PY - 2017/11

Y1 - 2017/11

N2 - Introduction: Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. Methods: We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis) and its subscores and correlation with disability and health scores. Results: The mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. Conclusions: Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901–911, 2017.

AB - Introduction: Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. Methods: We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis) and its subscores and correlation with disability and health scores. Results: The mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. Conclusions: Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901–911, 2017.

KW - disability

KW - familial amyloidotic polyneuropathy (FAP)

KW - neurophysiologic tests

KW - oligonucleotide trials

KW - peripheral neuropathy

KW - polyneuropathy signs

KW - proficiency

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